Long-term clinicopathological impact of calcineurin inhibitor cessation without specific cytoreductive induction in kidney transplantation

Clin Transplant. 2013 Nov-Dec:27 Suppl 26:9-13. doi: 10.1111/ctr.12274.

Abstract

Calcineurin inhibitors (CNIs) have considerably improved renal allograft survival. However, their chronic use has various adverse effects, including hypertension, hyperlipidemia, and nephrotoxicity. We conducted a retrospective study of kidney transplant recipients using a CNI withdrawal protocol. Eleven of 13 patients who had stable graft function on triple-drug therapy including a cyclosporine (CsA) were enrolled in this study. The dose of CsA was reduced by 20% every two wks until complete withdrawal. The mean period between the baseline and last biopsies was 97 (range: 21-123) months. No patient had an acute rejection episode during follow-up. Progression of interstitial fibrosis and tubular atrophy was seen in five and six cases, respectively. Arteriolar hyalinosis improved in three cases, but worsened in four. No patient lost his graft during the study. The mean serum creatinine level was 1.30 ± 0.26 mg/dL at baseline and stable for 10 yr after elimination (1.26 ± 0.11 mg/dL). At the end of the study, four of the eleven patients had reduced their antihypertensive drugs, and one patient had stopped hyperlipidemia treatment. CNI withdrawal can be implemented safely in stable renal transplant recipients and might lead to improved patient outcomes. Additional specific evidence of CNI nephrotoxicity should be elucidated.

Keywords: calcineurin inhibitor; kidney transplantation; pathology; toxicity.

MeSH terms

  • Adult
  • Azathioprine / administration & dosage
  • Calcineurin Inhibitors*
  • Cyclosporine / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Glucocorticoids / administration & dosage
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Kidney Diseases / etiology
  • Kidney Diseases / pathology
  • Kidney Diseases / surgery*
  • Kidney Transplantation*
  • Male
  • Methylprednisolone / administration & dosage
  • Middle Aged
  • Retrospective Studies
  • Young Adult

Substances

  • Calcineurin Inhibitors
  • Glucocorticoids
  • Immunosuppressive Agents
  • Cyclosporine
  • Azathioprine
  • Methylprednisolone